Tuberculosis is caused by the respiratory pathogen Mycobacterium tuberculosis and kills 2 million people each year, predominantly in the developing world. The only licensed vaccine against M. tuberculosis, bacille Calmette-Guerin (BCG) (Calmette, A., C. Guerin. (1924) Ann. Inst. Pasteur. 38:371), is an attenuated strain of Mycobacterium bovis, which in developing countries is typically administered intradermally as a single dose to newborn infants. Review of many studies suggests that BCG vaccination is protective against childhood meningeal tuberculosis and systemic forms of the disease. However, protective efficacy is variable (ranging from 0-80%) (Colditz, G. A. et al. (1994). JAMA 271:698) against adult pulmonary disease, the major global cause of tuberculosis mortality, and wanes with time (Sterne, J. A. et al. (1998) Int. J. Tuberc. Lung Dis. 2:200). The basis of the variability is uncertain. Even so, 80% of infants throughout the world receive BCG each year.
Mycobacterium tuberculosis is an intracellular pathogen, protective efficacy against which is associated with the maintenance of a strong cell-mediated response to infection involving both CD4+ and CD8+ T cells and the ability to respond with Th1-type cytokines, particularly IFN-γ (Flynn, J. L., J. Chan. (2001) Annu. Rev. Immunol. 19:93). BCG vaccination induces IFN-γ-secreting T cells, predominately of the CD4+ T cell phenotype, that cross-react with M. tuberculosis proteins (Launois P et al, (1994) Infection and Immunity 62(9):3679-87). Recent studies suggest that BCG delivered parenterally may fail to induce T cell immune responses in the lung mucosa, which may be critical for protection against pulmonary disease.
There is therefore a need to develop further vaccines against Mycobacterial disease.